A PROSPECTIVE-STUDY ON THE PROGNOSTIC-SIGNIFICANCE OF UROKINASE-TYPE PLASMINOGEN-ACTIVATOR LEVELS IN BREAST-CANCER TISSUE

Urokinase-type plasminogen activator (u-PA), which cleaves plasminogen to yield plasmin, is a serine protease of fibrinolysis and is presume d to play a key role in extracellular proteolysis and facilitate the m igration of cancer cells. This study was conducted prospectively to ev aluate the prognostic significance of u-PA antigen level in breast can cer tissues. u-PA concentrations in the cytosol of 226 breast cancer t issues were determined prospectively by enzyme-linked immunosorbent as say using cytosol fractions prepared for steroid hormone assay. The me dian follow-up period of the patients was 60 months. Various prognosti c factors were evaluated by univariate analysis or multivariate analys is using the Cox proportional-hazards method. Patients with primary br east cancer containing high levels of u-PA had a significantly shorter disease-free survival than patients with low levels of u-PA antigens. In multivariate analysis, a high level of u-PA was an independent ris k factor for disease-free survival, being independent of age, axillary node status, and estrogen receptor status. Among the major prognostic factors, a high u-PA antigen level, lymph node involvement, and a pos itive estrogen receptor status were the most important for predicting relapse-free survival (P = 0.044, P < 0.0001, P = 0.0039). This first prospective study confirmed the prognostic significance of the u-PA an tigen level in association with other major prognostic factors. The re sults of our present study suggest that u-PA in breast cancer tissue m ight be involved in breast cancer invasion and metastasis.